COPENHAGEN-Results of
the X-ACT trial of oral capecitabine
(Xeloda) vs fluorouracil/leucovorin
(5-FU/LV) as first-line adjuvant therapy
for metastatic colon cancer showed
that capecitabine had an improved
safety profile, compared with 5-FU/
LV, overall and in patients age 65 and
older. Christopher Twelves, MD, pro-
fessor of clinical cancer pharmacology,
University of Leeds and Tom Connors
Cancer Research Centre, Bradford,
UK, reported the results at ECCO
12, the European Cancer Conference.
The data have also been published inAnnals of Oncology (14:1735-1743,
2003).

The study randomized patients
with resected Dukes' C colon cancer
to receive 24 weeks of treatment with
either capecitabine 1,250 mg/m2 twice
daily on days 1 to 14 every 21 days (n
= 993) or IV bolus 5-FU 425 mg/m2
plus IV leucovorin 20 mg/m2 on days
1 to 5, repeated every 28 days (n =
974). Efficacy results are expected to
be available sometime this year.

In a planned safety analysis, patients
receiving capecitabine had significantly
less grade 3/4 neutropenia,
febrile neutropenia/sepsis, and stomatitis
(P < .001) but more grade 3
hand-foot syndrome than those treated
with 5-FU/LV. Capecitabine had a
similar, favorable safety profile in patients
less than 65 years of age and in
those 65 or older (see Table).

In their Annals of Oncology report,
the investigators stressed that "good
tolerability is a particularly important
consideration when chemotherapy is
administered in the adjuvant setting,"
especially considering recent results
from trials evaluating 5-FU/LV in combination
with irinotecan (Camptosar)
or oxaliplatin (Eloxatin).

For example, in the MOSAIC trial
comparing bolus/infusional 5-FU/LV
and oxaliplatin (FOLFOX4) vs infusional
5-FU/LV (the de Gramont regimen)
as adjuvant therapy for patients
with stage II-III colon cancer, FOLFOX4
produced a significant improvement
in 3-year disease-free survival
but, the investigators said, "at the expense
of a higher incidence of grade 3
or 4 neutropenia, and 29% of patients
experienced long-term (> 1 year) lowgrade
neurotoxicity."

The X-ACT researchers concluded
that in metastatic colon cancer
"capecitabine is an attractive agent to
replace 5-FU/LV as the backbone of
adjuvant combination treatment for
further studies."